Compositions and methods for disinfecting a contact lens and detecting the presence of an oxidative disinfectant

ABSTRACT

Compositions and methods useful for disinfecting a contact lens are disclosed. The present methods comprise contacting a contact lens with a liquid medium containing an effective amount of an oxidative disinfectant component at conditions to effectively disinfect the contact lens. The contacting occurs in the presence of a color indicator component which is soluble in the liquid medium and is adapted to provide a color indication of the presence of the oxidative disinfectant component in the liquid medium. The color indicator component comprises an effective amount of a transition metal component which is redox active, has an oxidized state of a first color and a reduced state of a different second color and a polyanionic component in an amount effective to inhibit the staining of the contact lens by the transition metal component.

BACKGROUND OF THE INVENTION

The present invention relates to compositions and methods useful indisinfecting a contact lens. More particularly, this invention relatesto such compositions and methods in which the presence of, andpreferably the substantial absence of, an oxidative disinfectant isindicated.

Contact lenses should be periodically disinfected by the user to preventinfection or other deleterious effects on ocular health which may beassociated with contact lens wear. Currently, there are severaldifferent conventional systems and methods which enable the user todisinfect his/her contact lenses between wearing times. Theseconventional cleaning and disinfection systems can be divided into "hot"and "cold" systems. Hot systems require the use of heat to disinfect thecontact lenses, whereas cold systems use chemical disinfectants atambient temperatures to disinfect the lenses.

Within the realm of cold disinfection systems are oxidativedisinfectant, in particular hydrogen peroxide, disinfection systems.Disinfecting hydrogen peroxide solutions are effective to kill thebacteria and fungi which may contaminate contact lenses. However,residual hydrogen peroxide on a disinfected contact lens may causeirritation, burning or other trauma to the eye unless this hydrogenperoxide is destroyed, i.e., decomposed, neutralized, inactivated orchemically reduced. Therefore, destruction of the residual hydrogenperoxide in the liquid medium containing the disinfected contact lens isneeded to enable safe and comfortable wear of the disinfected contactlens.

In order to avoid trauma to the eye caused by the presence of oxidativedisinfectant on or in the lens, it would be advantageous to have anindication of the presence of such oxidative disinfectant. Additionally,it would be advantageous to have an indication of the substantialabsence of such oxidative disinfectant, e.g., so that one would know itwas safe to place the disinfected lens into one's eye.

A number of soluble color indicators have been suggested for use incontact lens disinfecting service. See, for example, Huth et al U.S.Pat. No. 4,670,178 and Davies et al U.S. Pat. No. 4,863,627. The use ofsoluble color indicators has certain disadvantages. For example, thesoluble color indicator comes into intimate contact with the contactlens being treated and may have a detrimental effect on the lens and/oron the wearer of the lens.

Insoluble color indicators, such as those described in Amtower U.S. Pat.Nos. 5,362,444 and 5,395,621 are effective and advantageously keep thecontact lens separated from the active color indicator. One disadvantageof such insoluble indicators is that the response time to a change inthe concentration of oxidative disinfectant is relatively slow, whichcan result in unnecessary delays in placing disinfected lenses in thewearer's eyes or even placing active disinfectant in the lens wearer'seyes.

Color indication or indications of the presence and absence of hydrogenperoxide should be clear and distinct and should be provided in a timelymanner. Also, the color indicator component should be selected so thatthe lens and the lens wearer are not adversely affected.

There continues to be a need for a contact lens care system whicheffectively disinfects a contact lens and provides an indication of thepresence of the oxidative disinfectant so that the disinfected lens canbe safely and comfortably worn.

SUMMARY OF THE INVENTION

New compositions and methods for disinfecting, and preferably cleaning,contact lenses have been discovered. The present systems provide clear,positive and timely indications of the presence, and preferably of theabsence, of an oxidative disinfectant, preferably hydrogen peroxide, inthe lens disinfecting medium. The indication of the presence of anoxidative disinfectant warns the lens wearer not to place the lensdirectly from the oxidative disinfectant-containing medium into the eye.Importantly, the color indications are given in a timely manner. Thepresent color indicator components are safe, preferably are useful whenperoxidases, such as catalase, alone are used to destroy residualoxidative disinfectant, do not interfere with the disinfecting methodand have no substantial detrimental effect on the lens being disinfectedor on the wearer of the disinfected contact lens. The present inventiontakes advantage of the use of soluble color indicator components andcolor differences in transition metal components to provide theindication or indications noted herein. Such color differences areparticularly timely, clear and distinct, which greatly adds to theusefulness of the present system. Moreover, the present inventioneffectively provides for the use of transition metal components so thatconcerns regarding potential toxicity to the eye and contact lenscoloring or staining are substantially reduced, or even eliminated.

In one broad aspect, the present invention is directed to compositionsuseful in disinfecting a contact lens. Such compositions comprise aliquid medium, an oxidative disinfectant component and a color indicatorcomponent. The oxidative disinfectant component, preferably hydrogenperoxide, is present in an amount effective to disinfectant a contactlens immersed in the composition. The color indicator component issoluble in the liquid medium and is adapted and effective to provide acolor indication of the presence of the oxidative disinfectant componentin the liquid medium. The color indicator component comprises aneffective amount of a transition metal component which is redox active,has an oxidized state of a first color and a reduced state of adifferent second color and a polyanionic component present in an amounteffective to inhibit the staining of a contact lens immersed in thecomposition by the transition metal component. Preferably, thetransition metal component in the oxidized state is effective to providethe color indication of the presence of the oxidative disinfectantcomponent in the liquid medium.

In a particularly useful embodiment, the polyanionic component isselected from polymeric materials having multiple anionic charges andmixtures thereof. A particularly useful transition metal component isruthenium red.

In another broad aspect of the present invention, compositions areprovided which comprise at least one solid item including a colorindicator component. This color indicator component which is soluble ina liquid aqueous medium, is adapted to provide a color indication of thepresence, and preferably the absence, of an oxidative disinfectantcomponent in a liquid aqueous medium in which the composition is placed.The color indicator component comprises a transition metal componentwhich is redox active, has an oxidized state of a first color and areduced state of a different second color in an amount effective toprovide a color indication of the presence of an oxidative disinfectantcomponent in a liquid aqueous medium, and a polyanionic component in anamount effective to inhibit the staining of a contact lens immersed in aliquid aqueous medium containing the color indicator component in asolubilized form by the transition metal component. In a particularlyuseful embodiment, the solid item includes at least one of an effectiveamount of a contact lens cleaning enzyme component and an effectiveamount of an oxidative disinfectant destroying component. Preferably,the composition is structured to release the color indicator componentin a liquid aqueous medium prior to releasing the oxidative disinfectantdestroying component.

In a further broad aspect of the present invention, methods fordisinfecting a contact lens are provided. This method comprisescontacting a contact lens with a liquid medium containing an effectiveamount of an oxidative disinfectant component at conditions toeffectively disinfect a contact lens. This contacting occurs in thepresence of a color indicator component which is soluble in the liquidmedium. The color indicator component is adapted to provide a colorindication of the presence, and preferably the absence, of the oxidativedisinfectant component in the liquid medium. The color indicatorcomponent comprises an effective amount of a transition metal componentwhich is redox active, has an oxidized state of a first color and areduced color of a different second color and a polyanionic component inan amount effective to inhibit the staining of the contact lens by thetransition metal component.

These and other aspects of the present invention are apparent in thefollowing detailed description of the invention, examples and claims.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is of value where oxidative disinfectants, inparticularly hydrogen peroxide, are used to disinfect all types oflenses, e.g., contact lenses, which are benefitted by periodicaldisinfecting. Such lenses, e.g., conventional contact lenses, andpreferably soft contact lenses, may be made of any suitable material orcombination of materials and may have any suitable configuration notsubstantially deleteriously affected by such oxidative disinfectants.

Although any oxidative disinfectant component which is able toeffectively disinfect a contact lens may be employed in accordance withthe present invention, the much preferred oxidative disinfectant ishydrogen peroxide, especially aqueous solutions including hydrogenperoxide.

The color indicator component includes a transition metal component anda polyanionic component. The transition metal component is redox active,has an oxidized state of a first color and a reduced state of adifferent second color.

As used herein, the term "redox active" means that the component ormaterial in question is capable of being oxidized from a reduced stateto an oxidized state at the conditions present in a liquid aqueousmedium containing oxidative disinfectant component, and is capable ofbeing reduced from the oxidized state to the reduced state at theconditions present in the same liquid aqueous medium which issubstantially free of oxidative disinfectant component. Thus, thepresently useful transition metal components are present in an oxidizedstate in an oxidative disinfectant component-containing liquid aqueousmedium. After all the oxidative contact lens disinfectant component inthis liquid aqueous medium has been destroyed, for example, chemicallyreduced or decomposed, the transition metal component is present in theliquid aqueous medium in a reduced state.

Any transition metal component having the characteristics identifiedherein and suitable for functioning as part of the present colorindicator component may be employed in accordance with the presentinvention. The transition metal component preferably comprises a metalselected from ruthenium, other platinum group metals, cobalt, copper,chromium and the like and mixtures thereof. The transition metalcomponent may be incorporated into the present color indicator componentin any suitable form provided that such transition metal componentfunctions as described herein. Ruthenium red is a particularly usefultransition metal component.

The amount of transition metal component is sufficient to provide thedesired color indication or indications. For example, the transitionmetal component can be present in an amount in the range of about0.0001% by weight or less to about 1% or 2% by weight or more, based onthe weight of the liquid medium employed. Excessive amounts oftransition metal components should be avoided as being wasteful andbecause such amounts may have detrimental effects on the contact lensand/or the wearer of the contact lens.

Any suitable polyanionic component may be employed in accordance withthe present invention provided that it functions as described herein andhas no substantial detrimental effect on the contact lens beingdisinfected or on the wearer of the disinfected contact lens. Thepolyanionic component is preferably ophthalmically acceptable at theconcentrations used to inhibit staining of the contact lenses. Thepolyanionic component preferably includes three (3) or more anionic (ornegative) charges. In the event that the polyanionic component is apolymeric material, it is preferred that each of the repeating units ofthe polymeric material include a discrete anionic charge. Particularlyuseful anionic components are those which are water soluble, forexample, soluble at the concentrations used in the presently usefulliquid aqueous media, such as a liquid aqueous medium containing thepolyanionic component, the transition metal component and the oxidativedisinfectant component.

In one embodiment, the polyanionic component is sufficiently anionic tobe effective to form one or more complexes with the transition metalcomponent in a liquid medium, for example, a liquid aqueous medium.

A particularly useful class of polyanionic components are one or morepolymeric materials having multiple anionic charges. Examples include:

metal carboxymethylcelluloses

metal carboxymethylhydroxyethylcelluloses

metal carboxymethylstarchs

metal carboxymethylhydroxyethylstarchs

hydrolyzed polyacrylamides and polyacrylonitriles

heparin

homopolymers and copolymers of one or more of:

acrylic and methacrylic acids

metal acrylates and methacrylates

alginic acid

metal alginates

vinylsulfonic acid

metal vinylsulfonate

amino acids, such as aspartic acid, glutamic acid and the like

metal salts of amino acids

p-styrenesulfonic acid

metal p-styrenesulfonate

2-methacryloyloxyethylsulfonic acids

metal 2-methacryloyloxethylsulfonates

3-methacryloyloxy-2-hydroxypropylsulonic acids

metal 3-methacryloyloxy-2-hydroxypropylsulfonates

2-acrylamido-2-methylpropanesulfonic acids

metal 2-acrylamido-2-methylpropanesulfonates

allylsulfonic acid

metal allylsulfonate and the like.

The present polyanionic components often can exist in the un-ionizedstate, for example, in the solid state, in combination with a companionor counter ion, in particular a plurality of discrete cations equal innumber to the number of discrete anionic charges so that the un-ionizedpolyanionic component is electrically neutral. For example, the presentun-ionized polyanionic components may be present in the acid form and/orin combination with one or more metals. Since the polyanionic componentsare preferably ophthalmically acceptable, it is preferred that the metalassociated with the un-ionized polyanionic component be ophthalmicallyacceptable in the concentrations used. Particularly useful metalsinclude the alkali metals, for example, sodium and potassium, thealkaline earth metals, for example, calcium and magnesium, and mixturesthereof. Sodium is very useful to provide the counter ion in theun-ionized polyanionic component. Polyanionic components which, in theun-ionized states, are combined with cations other than H⁺ and metalcations can be employed in the present invention.

Particularly useful polyanionic components are selected from anioniccellulose derivatives, anionic polymers derived from acrylic acid(meaning to include polymers from acrylic acid, acrylates and the likeand mixtures thereof), anionic polymers derived from aspartic acid,anionic polymers derived from methacrylic acid (meaning to includepolymers from methacrylic acid, methacrylates, and the like and mixturesthereof), anionic polymers derived from alginic acid (meaning to includealginic acid, alginates, and the like and mixtures thereof), anionicpolymers derived from amino acids (meaning to include amino acids, aminoacid salts, and the like and mixtures thereof) and mixtures thereof.Very useful polyanionic components are those selected from anionicpolymers derived from aspartic acid, and mixtures thereof.

The amount of polyanionic component employed is that effective toinhibit the staining of a contact lens by the transition metalcomponent, as described herein. The specific amount of such componentused is not critical to the present invention provided that it functionsas a staining inhibitor, as described herein. In addition, the amount ofpolyanionic component employed depends on a number of factors, forexample, the specific polyanionic component being employed, the specifictransition metal component being employed and the specific transitionmetal component concentration being employed. In addition, excessiveamounts of polyanionic component are preferably to be avoided since thismay be wasteful and unnecessary and may have an adverse impact on thewearer of the disinfected contact lens. Preferably, the polyanioniccomponent is present in an amount of at least about 0.001% or at leastabout 0.005% to about 5% or about 2% or about 1%, based on the weight ofthe liquid disinfecting medium.

In a particularly useful embodiment, the weight ratio of polyanioniccomponent to transition metal component in the present color indicatorcomponents is preferably at least about 2, and more preferably in therange of about 4 to about 10 or about 20 or more.

Without wishing to limit the invention to any particular theory ofoperation, it is believed that the ratio of polyanionic component totransition metal component is important in order that the polyanioniccomponent be present in an amount effective to form water solublecomplexes with the transition metal component such that the transitionmetal component, in the complexed state, has a reduced propensity tostain the contact lens. In other words, it is believed that the presentpolyanionic component is preferably included in the present compositionsin amounts effective to form complexes which effectively inhibit thetransition metal component from staining the contact lens present in thecontact with the liquid aqueous medium.

In one embodiment, the present polyanionic components are combined withthe transition metal components in one or more solid particles, forexample, prior to use. To illustrate, a mixture containing a polyanioniccomponent and the transition metal component can be formed into asuitably sized and configured pill or tablet, for example, usingconventional techniques. When it is desired to disinfect a contact lens,the lens is placed into an oxidative disinfectant-containing liquidmedium, for example, a hydrogen peroxide-containing liquid aqueousmedium, together with the pill or tablet, which dissolves into theliquid medium. The contact lens is disinfected. In addition, thepolyanionic component is effective to inhibit staining of the contactlens by the transition metal component before, during and afterdisinfection. After the disinfectant component is effectively destroyed,the disinfected lens can be removed from the liquid medium and placeddirectly in the eye for safe and comfortable wear. Alternately, thedisinfected lens can be removed from the liquid medium, rinsed free ofthe liquid medium, for example, using a buffered saline, and then placedin the eye for safe and comfortable wear. The combination of transitionmetal component and polyanionic component effectively provides timelyindications of the presence and absence of oxidative disinfectantcomponent, without detrimentally affecting, e.g., staining the lens.

The liquid medium used in disinfecting a contact lens in the presentinvention preferably includes a disinfecting amount of oxidativedisinfectant, preferably hydrogen peroxide. Preferably, a disinfectingamount of oxidative disinfectant means such amount as will reduce themicrobial burden by one log in three hours. Still more preferably, thehydrogen peroxide concentration is such that the microbial load isreduced by one log order in one hour. Particularly preferred are thosehydrogen peroxide concentrations which reduce the microbial load by onelog unit in 10 minutes or less. Aqueous hydrogen peroxide solutions,preferably containing about 0.2% or about 0.5% to about 5% or about 6%of hydrogen peroxide (w/v), are known to be effective disinfectingsolutions for contact lenses. These solutions are effective at killingbacteria and fungi which may be found on contact lenses. Typically, theamount of hydrogen peroxide used in the liquid medium is well in excessof that required to effectively disinfect a contact lens. Substantialexcess hydrogen peroxide is used so that the lens disinfection can becompleted in a reasonable period of time.

The liquid medium used is selected to have no substantial detrimentaleffect on the lens being treated and to allow, and preferably to evenfacilitate, the present lens treatment or treatments. The liquid mediumis preferably aqueous-based. A particularly useful liquid aqueous mediumis that derived from saline, e.g., a conventional saline solution.During the disinfecting contacting, it is preferred that the liquidaqueous medium have a pH in the range of about 3 to about 9, morepreferably about 6 to about 8. The liquid medium, e.g., aqueous liquidmedium, preferably includes a buffer which is present in an amounteffective to maintain the pH of the liquid medium in the desired range.This buffer may be present in the liquid medium and/or may be introducedinto the liquid medium. Among the suitable buffers or buffering agentswhich may be employed are those which are conventionally used in contactlens care products. Examples of useful buffers include those withcarbonate functionalities, bicarbonate functionalities, phosphatefunctionalities, borate functionalities, and the like and mixturesthereof. The buffers may be alkali metal and alkaline earth metal salts,in particularly sodium and potassium.

In one embodiment, an oxidative disinfectant destroying component,hereinafter referred to as an ODDC, is included in a solid composition,e.g., a tablet, capsule, one or more solid particles and the like, whichis preferably introduced into the liquid medium about the same time asthe lens to be disinfected is introduced into the liquid medium. Suchsolid compositions include one or more ODDCs in an amount effective todestroy all the residual oxidative disinfectant remaining in the liquidmedium after the lens has been disinfected and preferably to reduce thepolymer matrix material and the transition metal component of the colorindicator component to the reduced states.

Thus, such preferred solid compositions, which are preferably initiallycontacted with the oxidative disinfectant-containing liquid medium atsubstantially the same time as is the lens to be disinfected, allow foreffective lens disinfection and, in addition, effectively destroy theresidual oxidative disinfectant remaining in the oxidativedisinfectant-containing liquid medium so that the disinfected lens canbe removed from the liquid medium and placed directly into the eye forsafe and comfortable wear. Preferably, the transition metal component ofthe color indicator component is also reduced and a second colorindication of the substantial absence of the oxidative disinfectant isprovided while the contact lens remains in the liquid medium, thusgiving added assurance to the lens wearer that it is safe to remove thelens from the liquid medium and to wear the disinfected lens. Suchpreferred compositions may be present in the form of at least one item,e.g., tablet, capsule, one or more solid particles and the like, whichincludes a coated portion, e.g., a core such as a core tablet, and abarrier component. The coated portion includes the ODDC or ODDCs fromthe coated portion into the liquid medium for a period of time,preferably sufficient to allow the lens to be disinfected. Preferably,the barrier coating substantially surrounds the coated portion.

Any suitable ODDC may be employed provided such ODDC has no substantialdetrimental effect on the present system, on the disinfected lens or onthe wearer of the disinfected lens. Among the useful ODDCs are oxidativedisinfectant reducing agents, peroxidases (meaning to include thereincatalase) and mixtures thereof.

Examples of the oxidative disinfectant reducing agents which are usefulin the present invention are alkali metal, in particular sodium,thiosulfates; thiourea; alkali metal, in particular sodium, formates;pyruvic acid and salts of pyruvic acid; N-acetylcysteine; ene-diolcompounds, e.g., ascorbic acid compounds, reductive acid compounds,isoascorbic acid compounds, glyoxylic acid compounds, squaric acidcompounds, dihydroxymaleic acid compounds, dihydroxyfumaric acidcompounds; and mixtures thereof. Typical examples of the foregoingene-diol compounds are the acids themselves, e.g., ascorbic acid,ophthalmically acceptable salts of such acids, e.g., sodium ascorbate,ophthalmically acceptable esters of such acids, e.g., ascorbic palmitateand any other ophthalmically acceptable derivatives of such acids, e.g.,that retain the ene-diol molecular structure, mixtures thereof and thelike. A particularly useful peroxidase is catalase. The peroxidases, andespecially catalase, are very beneficial in the present invention sincesuch ODDCs are effective to substantially eliminate hydrogen peroxidefrom a liquid medium in a reasonable period of time, e.g., on the orderof about 1 minute to about 12 hours, preferably about 5 minutes to about1 hour, after being initially released into the liquid medium.

The amount of ODDC employed is preferably sufficient to destroy all theoxidative disinfectant present in the liquid medium into which the ODDCis placed. Excess ODDC may be employed. Very large excesses of ODDC areto be avoided since the ODDC itself may cause problems with thedisinfected lens and/or the ability to safely and comfortably wear suchdisinfected lens. When catalase is employed as all or a part of theODDC, it is preferably present in an amount of about 100 to about 1000,more preferably about 150 to about 700 units of catalase activity permilliliter of liquid medium. For example, an especially useful amount ofcatalase for use in an aqueous solution containing about 3% (w/v)hydrogen peroxide is about 520 units of catalase activity/ml ofsolution.

The delayed release of the ODDC into the liquid medium may beaccomplished in any one of many suitable ways, a number of which areconventional and well known in the art. For example, a delayed releaseor barrier component, e.g., coating, may be provided by coating a coretablet, on other particles, containing the ODDC with a slow dissolvingcoating material, which may ultimately be completely or only partiallysoluble in the liquid medium, or by including the ODDC in a matrix fromwhich it may be slowly leached. Also, the matrix may be coated with aslow dissolving material so that the start of the slow release isdelayed. The delayed release form of the ODDC is preferably such thatsubstantially no release occurs during a delay period followed by rapidand substantially complete release of the ODDC at the end of the delayperiod. Such a result may be obtained by coating the ODDC with a slowdissolving coating.

Although multi-layered (including core and one or more coating layers)tablets or pills are preferred, the delayed release form of the presentcompositions can be present in any other suitable item or items, such asmasses of powders, granules and the like. Delayed release technology iswell known in the art as exemplified by the text Controlled DrugDelivery, 2nd Ed., Joseph R. Robinson & Vincent H. L. Lee, Eds., MarcelDekker, Inc., New York, 1987.

Any suitable delayed release component or combination of delayed releasecomponents may be employed, provided that such component or componentsfunction as described herein and have no substantially detrimentaleffect on the other components present, on the lens being treated and onthe human wearing the treated lens. The delayed release component ispreferably at least partially, more preferably completely, watersoluble. The delayed release component preferably comprises a majoramount of at least one polymeric material.

Delayed release or barrier components suitable as either coatings or asmatrices, include water soluble vinyl polymers, such aspolyvinylpyrrolidone, polyvinylalcohol and polyehtyleneglycol; watersoluble proteins; polysaccharide and cellulose derivatives, such asmethyl cellulose and hydroxypropylmethyl cellulose; and the like andmixtures thereof.

The amount of delayed release or barrier component used is not criticalin the present invention provided that such component functions asdescribed herein. The delayed release or barrier component may suitablybe present in the range of about 1% to about 20% or more, based on theweight of the ODDC.

The solid compositions may be produced using any one of many suitablemethods, a number of which are conventional and well known in the art.

The solid compositions may include other components, for example,fillers, binders, tonicity agents, contact lens conditioning/wettingagents, buffering agents, lubricating agents and the like. Each of thesecomponents may be present, if at all, in an amount effective to performits designated function or functions. Examples of each of these types ofcomponents are conventional and well known in the art. Therefore, adetailed description of such components is not presented here.

In a particularly useful embodiment, the contact lens may be subjectedto the action of at least one enzyme effective to remove debris from acontact lens. Among the types of debris that form on contact lens duringnormal use are protein-based debris, mucin-based debris, lipid-baseddebris and carbohydrate-based debris. One or more types of debris may bepresent on a single contact lens.

The enzyme employed may be selected from peroxide-active enzymes whichare conventionally employed in the enzymatic cleaning of contact lenses.For example, many of the enzymes disclosed in Huth et al U.S. Pat. No.4,670,178 are useful in the present invention. The disclosure of thispatent is incorporated in its entirety by reference herein. Among theuseful enzymes are those selected from proteolytic enzymes, lipases andmixtures thereof.

Preferred proteolytic enzymes are those which are substantially free ofsulfhydryl groups or disulfide bonds, whose presence may react with theactive oxygen of the disinfectant to the detriment of the activity ofthe enzymes. Metallo-proteases, those enzymes which contain a divalentmetal ion such as calcium, magnesium or zinc bound to the protein, mayalso be used.

A more preferred group of proteolytic enzymes are the serine proteases,particularly those derived from Bacillus and Streptomyces bacterial andAspergillus molds. Within this grouping, the still more preferredenzymes are the derived alkaline proteases generically called subtilisinenzymes. Reference is made to Deayl, L., Moser, P. W. and Wildi, B. S.,"Proteases of the Genus Bacillus. II Alkaline Proteases", Biotechnologyand Bioengineering, Vol. XII, pp. 213-249 (1970) and Deayl, L. andMoser, P. W., "Differentiation of Alkaline Proteases Form BacillusSpecies" Biochemical and Biophysical Research Comm., Vol. 34, No. 5, pp.600-604 (1969).

The subtilisin enzymes are broken down into two sub-classes, subtilisinA and subtilisin B. In the subtilisin A grouping are enzymes derivedfrom such species as B. subtilis, B. licheniformis and B. pumilis.Organisms in this sub-class produce little or no neutral protease oramylase. The subtilisin B sub-class is made up of enzymes from suchorganisms as B. subtilis, B. subtilis var. amylosacchariticus, B.amyloliquefaciens and B. subtilis NRRL B3411. These organisms produceneutral proteases and amylases on a level about comparable to theiralkaline protease production. One or more enzymes from the subtilisin Asub-class are particularly useful.

In addition, other preferred enzymes are, for example, pancreatin,trypsin, collagenase, keratinase, carboxylase, aminopeptidase, elastase,and aspergillo-peptidase A and B, pronase E (from S. griseus) anddispase (from Bacillus polymysxa).

If such an enzyme or enzymes are employed, an effective amount ispreferably used. Such amount will be that amount which effects removalin a reasonable time (for example overnight) of substantially all of atleast one type of debris from a lens due to normal wear. This standardis stated with reference to contact lens wearers with a history ofnormal pattern of lens debris accretion, not the very small group whomay at one time or another have a significantly increased rate of debrisaccretion such that cleaning is recommended every day, or every two orthree days.

The amount of enzyme required to make an effective cleaner will dependon several factors, including the inherent activity of the enzyme, andthe extent of its interaction with the hydrogen peroxide present.

As a basic yardstick, the working solution should contain sufficientenzyme to provide about 0.001 to about 3 Anson units of activity,preferably about 0.01 to about 1 Anson units of activity, preferablyabout 0.01 to about 1 Anson units, per single lens treatment. Higher orlower amounts may be used.

Enzyme activity is pH dependent so for any given enzyme, there is aparticular pH range in which that enzyme will function best. Thedetermination of such range can readily be done by known techniques.

Solid compositions which include such lens cleaning enzymes may bestructured to release the enzyme, into the liquid medium which contactsthe composition, at any time relative to the other component orcomponents of the composition provided that the released enzyme iseffective at the conditions present in the liquid medium to perform thecleaning function, as described herein. In one particularly usefulembodiment, the cleaning enzyme is released into the liquid mediumsubstantially immediately upon introducing the solid composition intothe liquid medium.

In the event that a debris removing enzyme is present, the contact lensin the liquid medium is effectively cleaned of such debris. Thiscleaning action can occur before the lens is disinfected, at the timethe lens is being disinfected, or after the lens is disinfected.

The disinfecting contacting preferably occurs at a temperature tomaintain the liquid medium substantially liquid. It is preferred thatthe contacting temperature be in the range of about 0° C. to about 100°C., and more preferably in the range of about 10° C. to about 60° andstill more preferably in the range of about 15° C. to about 30° C.Contacting at or about ambient temperature is very convenient anduseful. The contacting preferably occurs for a time to substantiallycompletely disinfect the lens being treated. Such contacting times canbe in the range of about 1 minute to about 12 hours or more.

After such contacting, the liquid medium preferably includessubstantially no residual, oxidative disinfectant and the disinfectedlens can be removed from this liquid medium and placed directly into theeye for safe and comfortable wear. However, if the liquid mediumincludes one or more "cleaning" enzymes, it is preferred to rinse thedisinfected lens, e.g., with saline, to free the lens of such enzymeprior to placing the disinfected lens into the eye.

The following non-limiting examples illustrate certain aspects of thepresent invention.

EXAMPLE 1

Aqueous hydrogen peroxide solutions were added to a combination ofruthenium red (10 ppm by weight of the solution) and poly(aspartic acid)(100 ppm by weight of the solution). Color changes of these solutionsare summarized in the following table:

    ______________________________________                                        H.sub.2 O.sub.2                                                                         COLORS/COLOR CHANGE                                                                            TIME TO CHANGE                                     ______________________________________                                        0.3% (w/v)                                                                              pink to yellow   instantaneously                                    0.03% (w/v)                                                                             pink to yellow   instantaneously                                    0.003% (w/v)                                                                            pink to yellow   5 minutes                                          0.0003% (w/v)                                                                           pink             did not change                                     ______________________________________                                    

These results demonstrate that the response time of the color indicators(soluble ruthenium red) was very rapid and effectively indicated thepresence of hydrogen peroxide above 0.0003% (w/v) concentration.

EXAMPLE 2

Contact lenses, made of an ionic, high water content hydrogel material,were soaked in phosphate buffered saline (pH 7.4) containing 10 ppm byweight of the solution of ruthenium red and ethylenediaminetetraaceticacid or citric acid at various concentrations. All lenses were stainedby ruthenium red within one hour. When the same test was attempted withsodium hexametaphosphate, the ruthenium red was decomposed and nostaining experiment could be done.

EXAMPLE 3

Contact lenses, made of an ionic, high water content hydrogel material,were soaked in phosphate buffered saline (pH 7.4) containing 20 ppm byweight of the solution of ruthenium red and poly(acrylic acid) (PAA) atvarious concentrations. Staining on the lenses were checked periodicallyand results are summarized in the following table:

    ______________________________________                                        Poly(Acrylic Acid),                                                           ppm by weight of solution                                                                     TIME, hours  LENS COLOR                                       ______________________________________                                        0               3            pink                                             50              3            clear                                            50              6            clear                                            100             3            clear                                            100             6            clear                                            ______________________________________                                    

The solutions of ruthenium red and poly(acrylic acid) lost their pinkcolor in a couple of days and no long term observations on the stainingof lenses were made.

EXAMPLE 4

Contact lens, made of an ionic, high water content hydrogel material,were soaked in phosphate buffered saline (pH 7.2) containing 8 ppm byweight of the solution of ruthenium red and poly(aspartic acid) (PASP)at various concentrations. Staining of lenses by rhthenium red waschecked periodically and the results are summarized in the followingtable:

    ______________________________________                                        (Poly Aspartic Acid),                                                         ppm by weight of solution                                                                      TIME, hours  Lens Color                                      ______________________________________                                        0                2 hours      pink                                             40 ppm          2 hours      pink                                             80 ppm          2, 8 and 24 hrs.                                                                           clear                                           100 ppm          2, 8 and 24 hrs.                                                                           clear                                           120 ppm          2, 8 and 24 hrs.                                                                           clear                                           ______________________________________                                    

EXAMPLE 5

This experiment was a continuation of Example 4. Similar lenses in thebuffered saline were kept in the dark (ruthenium red is light sensitive)at room temperature for the long term observation. The saline containingruthenium red and poly(aspartic acid) maintained the pink color for fourmonths. The lenses were checked for staining periodically and theresults are summarized in the following table:

    ______________________________________                                        (Poly Aspartic Acid),                                                         ppm by weight of solution                                                                      TIME, days  Lens Color                                       ______________________________________                                        0                30, 60 and 120                                                                            pink                                              80 ppm          30, 60 and 120                                                                            clear                                            100 ppm          30, 60 and 120                                                                            clear                                            120 ppm          30, 60 and 120                                                                            clear                                            ______________________________________                                    

EXAMPLE 6

A contact lens, made of a nonionic, high water content hydrogelmaterial, was soaked in phosphate buffered saline containing 4 ppm byweight of the solution of ruthenium red and 40 ppm by weight of thesolution of poly(aspartic acid). A second, similar contact lens wassoaked in a similar buffered saline containing 4 ppm by weight of thesolution of ruthenium red and 80 ppm by weight of the solution ofpoly(aspartic acid). Both lenses remained clear even after four monthsin the dark at room temperature while the solutions maintained theirpink color.

EXAMPLE 7

A pair of protein-based debris laden contact lenses are placed in aconventional lens vial. 10 ml of a saline solution containing 3% (w/v)of H₂ O₂, 0.3% by weight of boric acid, 10 ppm by weight of the solutionof ruthenium red and 100 ppm by weight of the solution of poly(asparticacid) is added to the vial so that the contact lenses are completelysubmerged in the solution. The pH of this solution is about 7.5. At thispoint the solution is yellow in color.

A layered, delayed release tablet is dropped into the solution in thelens vial. The center core of the tablet includes 2.0 mg of crystallinecatalase. The outer layer of the tablet includes 0.4 mg of subtilisin Aenzyme. A delayed release layer between the inner layer and the outerlayer is structured and designed to dissolve sufficiently in two hoursafter being exposed to the solution in the lens vial to release thecatalase into the solution.

Upon being dropped into the solution, the outer layer of the tabletdissolves to release the subtilisin A into the solution. The enzyme inthe outer layer begins to attack and remove the protein-based debris onthe lenses. Substantially all of the protein-based debris is removedfrom the lenses. In addition, the contact lenses are effectivelydisinfected. Two hours after the layered tablet is first dropped intothe solution, the catalase is released into the solution and destroysthe residual hydrogen peroxide in the solution and the ruthenium red isreduced to a reduced state. The solution turns pink in color.

Upon seeing the pink solution, the lens wearer removes thecleaned/disinfected lenses from the solution, rinses them withphysiological saline solution to remove the subtilisin A enzyme, andplaces them in his/her eyes. It is found that the contact lenses areeffectively disinfected and cleaned of protein-based debris. The lenswearer experiences no discomfort or eye irritation from wearing thedisinfected and cleaned contact lenses.

EXAMPLE 8

A pair of protein-based debris laden contact lenses are placed in aconventional lens vial. 10 ml of a saline solution containing 3% (w/v)of H₂ O₂ and 0.3% by weight of boric acid is added to the vial so thatthe contact lenses are completely submerged in the solution. The pH ofthis solution is about 7.5.

A layered, delayed release tablet is dropped into the solution in thelens vial. The center core of the tablet includes 2.0 mg of crystallinecatalase. The outer layer of the tablet includes 0.4 mg of subtilisin Aenzyme, 0.1 mg of ruthenium red and 1.0 mg of poly(aspartic acid). Adelayed release layer between the inner layer and the outer layer isstructured and designed to dissolve sufficiently in two hours afterbeing exposed to the solution in the lens vial to release the catalaseinto the solution.

Upon being dropped into the solution, the outer layer of the tabletdissolves to release the subtilisin A into the solution. At this point,the solution is yellow in color. The enzyme in the outer layer begins toattack and remove the protein-based debris on the lenses. Substantiallyall of the protein-based debris is removed from the lenses. In addition,the contact lenses are effectively disinfected. Two hours after thelayered tablet is first dropped into the solution, the catalase isreleased into the solution and destroys the residual hydrogen peroxidein the solution and the ruthenium red is reduced to a reduced state. Thesolution turns pink in color. Upon seeing the pink solution, the lenswearer removes the cleaned-disinfected lenses from the solution, rinsesthem with physiological saline solution to remove the subtilisin Aenzyme, and places them in his/her eyes. It is found that the contactlenses are effectively disinfected and cleaned of protein-based debris.The lens wearer experiences no discomfort or eye irritation from wearingthe disinfected and cleaned contact lenses.

While this invention has been described with respect to various specificexamples and embodiments, it is to be understood that the invention isnot limited thereto and that it can be variously practiced within thescope of the following claims.

What is claimed is:
 1. A composition comprising:a liquid aqueous medium;hydrogen peroxide in an amount of about 0.2% to about 6% (w/v) of saidcomposition effective to disinfect a contact lens immersed in saidcomposition; and a color indicator component which is soluble in saidliquid aqueous medium and is effective to provide a color indication ofthe presence of said hydrogen peroxide in said liquid aqueous medium,said color indicator component comprising about 0.0001% to about 2% byweight of said liquid aqueous medium of a transition metal componentwhich is redox active, has an oxidized state of a first color, a reducedstate of a different second color and comprises a metal selected fromthe group consisting of ruthenium, other platinum group metals, cobalt,chromium and mixtures thereof and about 0.001% to about 5% by weight ofsaid liquid aqueous medium of a polyanionic component selected from thegroup consisting of anionic cellulose derivatives, anionic acrylic acidpolymers, anionic aspartic acid polymers, anionic glutamic acidpolymers, anionic alginic acid polymers, anionic dextran derivatives andmixtures thereof effective to inhibit the staining of a contact lensimmersed in said composition by said transition metal component.
 2. Thecomposition of claim 1 wherein said transition metal component in saidoxidized state is effective to provide said color indication of thepresence of said hydrogen peroxide in said liquid aqueous medium.
 3. Thecomposition of claim 1 wherein said polyanionic component is selectedfrom the group consisting of anionic aspartic acid polymers and mixturesthereof.
 4. The composition of claim 1 wherein said polyanioniccomponent is effective to form one or more complexes with saidtransition metal component in said liquid aqueous medium.
 5. Thecomposition of claim 1 wherein said transition metal component isruthenium red. component.
 6. The composition of claim 1 wherein saidpolyanionic component is selected from the group consisting of anionicacrylic acid polymers, anionic aspartic acid polymers and mixturesthereof.
 7. The composition of claim 1 wherein said transition metalcomponent comprises a metal selected from the group consisting ofruthenium, other platinum group metals and mixtures thereof.
 8. Thecomposition of claim 1 wherein said transition metal component comprisesruthenium.
 9. A composition comprising at least one solid item includinga color indicator component which is soluble in a quantity of liquidaqueous medium containing hydrogen peroxide effective to disinfect acontact lens immersed therein and is effective to provide a colorindication of the presence of hydrogen peroxide in the quantity ofliquid aqueous medium, said color indicator component comprising atransition metal component which is redox active, has an oxidized stateof a first color, a reduced state of a different second color andcomprises a metal selected from the group consisting of ruthenium, otherplatinum group metals, cobalt, chromium and mixtures thereof effectiveto provide a color indication of the presence of hydrogen peroxide inthe quantity of liquid aqueous medium, and a polyanionic componentselected from the group consisting of anionic cellulose derivatives,anionic acrylic acid polymers, anionic aspartic acid polymers, anionicglutamic acid polymers, anionic alginic acid polymers, anionic dextranderivatives and mixtures thereof effective to inhibit the staining of acontact lens immersed in the quantity of liquid aqueous mediumcontaining said color indicator component in a solubilized form by saidtransition metal component, the weight ratio of said polyanioniccomponent to said transition metal component being at least about
 2. 10.The composition of claim 9 wherein said at least one solid item furtherincludes an effective amount of a contact lens cleaning enzymecomponent.
 11. The composition of claim 9 wherein said at least onesolid item further includes an effective amount of a hydrogen peroxidedestroying component.
 12. The composition of claim 11 which isstructured to release said color indicator component in the quantity ofliquid aqueous medium prior to said hydrogen peroxide destroyingcomponent.
 13. The composition of claim 9 wherein said polyanioniccomponent is selected from the group consisting of anionic acrylic acidpolymers, anionic aspartic acid polymers and mixtures thereof.
 14. Thecomposition of claim 9 wherein said transition metal component comprisesa metal selected from the group consisting of ruthenium, other platinumgroup metals and mixtures thereof.
 15. The composition of claim 9wherein said transition metal component is ruthenium red.
 16. Acomposition comprisinga liquid aqueous medium; hydrogen peroxide in anamount of about 0.2% to about 6% (w/v) of said composition effective todisinfect a contact lens immersed in said composition; and a colorindicator component which is soluble in said liquid aqueous medium andis effective to provide a color indication of the presence of saidhydrogen peroxide in said liquid aqueous medium, said color indicatorcomponent comprising ruthenium red in an amount in the range of about0.0001% to about 2% by weight, based on the weight of said liquidaqueous medium and a polyanionic component selected from the groupconsisting of anionic acrylic acid polymers, anionic aspartic acidpolymers and mixtures thereof in an amount in the range of about 0.0001%to about 5% by weight, based one the weight of said liquid aqueousmedium, effective to inhibit the staining of a contact lens immersed insaid composition by said ruthenium red.
 17. The composition of claim 16wherein said polyanionic component is selected from the group consistingof anionic aspartic acid polymers and mixtures thereof.
 18. Thecompositions of claim 16 wherein said polyanionic component is effectiveto form one or more complexes with said ruthenium red in said liquidaqueous medium.
 19. A composition comprising at least one solid itemincluding a color indicator component which is soluble in a quantity ofliquid aqueous medium containing hydrogen peroxide effective todisinfect a contact lens immersed therein and is effective to provide acolor indication of the presence of hydrogen peroxide in the quantity ofliquid aqueous medium, said color indicator component comprisingruthenium red and a polyanionic component selected from the groupconsisting of anionic acrylic acid polymers, anionic aspartic acidpolymers and mixtures thereof effective to inhibit the staining of acontact lens immersed in the quantity of liquid aqueous mediumcontaining the color indicator component in a solubilized from by saidruthenium red, the weight ratio of said polyanionic component toruthenium red being at least about
 2. 20. The composition of claim 19wherein said polyanionic component is selected from the group consistingof anionic aspartic acid polymers and mixtures thereof.